How Long Should we Give Steroids for Patients With Severe PCP (HOW LONG)

How Long Should we Give Steroids for Patients With Severe PCP (HOW LONG)

The HOW LONG trial is an international, multicenter, Phase IV randomized clinical trial evaluating the optimal duration of adjunctive systemic corticosteroids in immunocompromised adults with severe Pneumocystis jirovecii pneumonia (PCP) who demonstrate early clinical recovery. Participants who no longer require supplemental oxygen by day 10 of corticosteroid therapy are randomized to discontinue corticosteroids at day 10 (or hospital discharge, if earlier) versus continue corticosteroids for a total of 21 days. The trial assesses whether earlier discontinuation reduces steroid-related complications while maintaining clinical outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Pneumocystis Jirovecii Infection; Pneumocystis; Pneumocystis Pneumonia; Pneumocystosis; Pneumonia (Etiology); Pneumocystis Carinii; Infection, Resulting From HIV Disease; Pneumocystosis Associated With AIDS; Pneumocystis Jiroveci Pneumonia
• Intervention / Treatment: Drug: Systemic corticosteroids

Detailed Description

Adjunctive systemic corticosteroids are routinely used in severe PCP to reduce pulmonary inflammation and improve survival, but the recommended 21-day duration is based on limited historical evidence. Prolonged corticosteroid exposure may increase risks including secondary infections, hyperglycemia, gastrointestinal bleeding, and other adverse effects. The HOW LONG trial tests whether stopping corticosteroids earlier, after clinical recovery, improves net clinical outcomes.

Eligible adults with proven or probable severe PCP who have recovered to room air (no need for supplemental oxygen) for at least 6 hours by day 10 of corticosteroid therapy are enrolled and randomized centrally 1:1 in the MUHC Research Electronic Data Capture (REDCap) system to (1) discontinuation of corticosteroids at day 10 or hospital discharge or (2) continuation of corticosteroids to a total of 21 days. All participants receive standard antimicrobial therapy for PCP per treating clinicians. Follow-up occurs to day 180.

The primary endpoint is a hierarchical composite outcome assessed at day 60, incorporating mortality, relapse of PCP-related hypoxemia, secondary infections, severe metabolic or gastrointestinal complications, and length of hospital stay. Secondary endpoints include individual components of the composite outcome, and tertiary endpoints include quality of life and longer-term outcomes through day 180.

• Study Type: Interventional
• Enrollment (Estimated): 416
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Babykumari Chitramuthu, PhD; Phone Number: 23730 15149341934; Email: babykumari.chitramuthu@muhc.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill university Health Centre (Royal victoria Hospital and Montreal General Hospital
      • Principal Investigator: Emily G McDonald, MD MSc
      • Principal Investigator: Todd C Lee, MD MPH FIDSA
      • Contact: Babykumari Chitramuthu, PhD; Phone Number: 23730 5149341934; Email: babykumari.chitramuthu@muhc.mcgill.ca
      • Principal Investigator: Matthew P Cheng, MDCM, FRCPC, FACP, DABMM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Proven or probable Pneumocystis jirovecii pneumonia
• Severe PCP requiring supplemental oxygen (e.g., ≥4 L/min or ≥35% FiO₂ to maintain SpO₂ ≥94%)
• Planned or receiving adjunctive systemic corticosteroid therapy for severe PCP
• Clinical recovery by day 10 of steroid therapy: breathing room air for ≥6 hours
• Able to provide informed consent (or per local requirements)

Exclusion Criteria:

• Persistent hypoxemia or ongoing oxygen requirement at day 10
• Clinical deterioration prior to randomization
• Treating clinician determines steroids must be continued or stopped immediately for medical reasons
• Anticipated death within 48 hours
• Inability or unwillingness to complete follow-up through day 180

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Shortened-Duration Corticosteroids; Discontinue adjunctive systemic corticosteroids at day 10 of therapy or at hospital discharge (whichever occurs first), after documented clinical recovery (room air for ≥6 hours).	Drug: Systemic corticosteroids; Adjunctive systemiccorticosteroid therapy administered as part of standard treatment for pneumocystis Pneumonia, with duration varying by study arm.
Active Comparator: Standard duration of Corticosteroids; Continue adjunctive systemic corticosteroids to a total of 21 days (standard of care).	Drug: Systemic corticosteroids; Adjunctive systemiccorticosteroid therapy administered as part of standard treatment for pneumocystis Pneumonia, with duration varying by study arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hierarchical composite clinical outcome	The primary outcome at day 60 will be the hierarchical composite of: death,; relapse of PCP-related hypoxemia (e.g., not due to another obviously identified cause like pulmonary embolism, aspiration event, etc.) requiring more than 12 hours of use of ≥2L of oxygen in accordance with guidelines; The development of secondary infections requiring systemic antibiotic therapy; The development of severe diabetic complications (ketoacidosis, hyperosmolar coma, new initiation of insulin which is continued at discharge); The development of severe GI bleeding (e.g., necessitating unplanned transfusion and/or endoscopy) and;; inpatient length of stay (censored at day 60; deaths assigned 60 days).	Day 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	Mortality at day 60	Day 60
relapse of PCP-related hypoxemia	(Relapse of PCP-related hypoxemia that is not due to another obviously identified cause like pulmonary embolism, aspiration event, etc.) requiring more than 12 hours of use of ≥2L of oxygen in accordance with guidelines	Day 60
Secondary infections requiring systemic antibiotic therapy	The development of secondary infections requiring systemic antibiotic therapy	Day 60
The development of severe diabetic complications	Severe complications of diabetes include: ketoacidosis, hyperosmolar coma, new initiation of insulin which is continued at discharge	Day 60
The development of severe GI bleeding (	Gastrointestinal bleeding necessitating unplanned transfusion and/or endoscopy	Day 60
inpatient length of stay (censored at day 60; deaths assigned 60 days).	inpatient length of stay censored at day 60; deaths assigned 60 days.	Day 60

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life (EQ-5D-5L)	Higher score indicates better quality of life	Day 30
Quality of life (EQ-5D-5L)	Higher score indicates better quality of life	Day 180
All-cause mortality	all cause mortality	Day 180
PCP recurrence	recurrence of PCP infection following the initial infection	Day 180

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

General Publications

• Senecal J, Smyth E, Del Corpo O, Hsu JM, Amar-Zifkin A, Bergeron A, Cheng MP, Butler-Laporte G, McDonald EG, Lee TC. Non-invasive diagnosis of Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. Clin Microbiol Infect. 2022 Jan;28(1):23-30. doi: 10.1016/j.cmi.2021.08.017. Epub 2021 Aug 28.
• McDonald EG, Butler-Laporte G, Del Corpo O, Hsu JM, Lawandi A, Senecal J, Sohani ZN, Cheng MP, Lee TC. On the Treatment of Pneumocystis jirovecii Pneumonia: Current Practice Based on Outdated Evidence. Open Forum Infect Dis. 2021 Oct 29;8(12):ofab545. doi: 10.1093/ofid/ofab545. eCollection 2021 Dec.

Study record dates

Study Major Dates

• Study Start (Estimated): January 30, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: December 15, 2025
• First Submitted That Met QC Criteria: December 27, 2025
• First Posted (Actual): January 9, 2026

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: December 27, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: HIV; Randomized Control Trial; PCP; Non-HIV; Immunocompromised host; Pneumocystis jirovecii pneumonia; Systemic Corticosteroids; De-escalation of Therapy
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections and Mycoses; Lung Diseases, Fungal; Mycoses; Pneumonia; Infections; Pneumonia, Pneumocystis; Pneumocystis Infections
• Other Study ID Numbers: 2026-12265; 527077 (Other Grant/Funding Number: CIHR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized data will be made available upon reasonable request to the principal investigator by email (emily.mcdonald@mcgill.ca) subject to discussion surrounding the necessity of an interinstitutional data sharing agreement, commencing one year following the publication of the main trial results, for a period of 2 years.
• IPD Sharing Time Frame: 1 year following main publication for a period of 2 years
• IPD Sharing Access Criteria: investigators wishing to pursue secondary questions related to the data can contact emily.mcdonald@mcgill.ca for access to the data via a data sharing agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No